In addition to the neuropsychological and behavioral disorders inherent in fetal alcohol syndrome (FAS), significant impairments in immune function have been identified in these patients. FAS children have an increased incidence of bacterial infections including, but not limited to, meningitis, pneumonia and sepsis, as well as increased viral infections caused by agents such as cytomegalovirus and influenza. In spite of what is known about the consequences of fetal alcohol exposure, up to 30% of women report consuming alcohol during their pregnancy and the prevalence of FAS in the United States remains between 0.2-1.5 in every 1000 live births. Additionally, children diagnosed with FAS incur annual mean medical expenditures nine times as high as those of children without FAS. The goal of the proposed studies is to evaluate the effects of alcohol exposure on the human immune system, specifically on regulatory T cells (Tregs) and a Treg inducing monocyte subset. Tregs are critical in the human immune system by maintaining self tolerance and immune homeostasis. However, an increased frequency of Tregs or an aberrant activation of this subset is capable of suppressing immune responses against invading pathogens such as bacteria and viruses. We have identified a population of monocytes present in human cord blood that is sufficient to induce Treg differentiation from native CD4+ T cells. This Treg inducing subset is characterized by their high expression of both the myeloid lineage marker CD14 and the scavenger receptor CD36 (CD36HI monocytes). Lipopolysaccharide (LPS) pretreatment of CD36HI monocytes abrogates their ability to promote Treg induction. Literature suggests that alcohol exposure can alter aspects of human Treg biology including expression of Foxp3, a transcription factor required and sufficient for Treg differentiation and function. Additionally, literature reports alcohol induced alterations in human monocyte biology. We hypothesize that alcohol exposure significantly increases human Treg induction and alters the phenotype and function of the Treg inducing CD36HI monocyte subset before and after LPS exposure. To address this hypothesis, the following specific aims are proposed using mononuclear cells enriched from human cord blood: (1) to characterize the effects of alcohol on Treg induction and (2) to determine the effects of alcohol on the Treg inducing CD36HI monocyte subset before and after LPS treatment. The proposed aims will potentially elucidate a novel influence of alcohol on both human Tregs and CD36HI monocytes. These data will significantly progress our understanding of the immune deficiencies seen in FAS, as an alcohol induced alteration in Treg induction may account for the FAS neonate's decreased ability to respond to foreign infectious agents. The proposed studies could elucidate novel therapeutic avenues to treat the immunopathology associated with FAS.